The recent case report of an HIV-infected child in Mississippi with viral control post-antiretroviral therapy (ART) interruption has sparked interest in the possibility of 'functional cure' in infants if they initiate ART very soon after birth. The 'Mississippi baby' also raises many new questions around the clinical care of HIV-infected infants and young children, including when treatment should be initiated, why treatment should be initiated, what treatment should be initiated, and how to identify infants early enough to treat them adequately. Here, we review research conducted before the report of the 'Mississippi baby' highlighting the important new issues that now need to be taken into consideration.